This project seeks to elucidate mechanisms whereby lymphocytes kill some, but not all, tumor cells in the absence of detectable humoral antibody. The neoplastic cells to be used will consist mostly of human melanoma cell lines already shown in vitro to be either sensitive (S) or resistant (R) to lysis by preparations of blood lymphocytes enriched specifically for cells bearing receptors for the Fc portion of IgG and/or by cells which have the morphology of large granular lymphocytes, i.e., enriched for natural killer cells. Membrane properties of the target cells will be analyzed for surface enzymes, Ia antigen, fibronectin, lectin receptors and a variety of ultrastructural properties including those revealed by freeze-cleavage, to determine whether differences exist between S and R targets. Preparations enriched for human natural killer cells will be obtained by gradient centrifugation, and such cells will be identified by ultrastructural and histochemical criteria already defined in this laboratory as well as by other investigators. The initial event which eventuates in tumor cell lysis will be explored by histochemical and ultrastructural studies of target-effector cell conjugates. The project has been stimulated by the observation that mononuclear cell infiltrates in the lesions constituting malignant melanoma signify a more favorable prognosis. Therefore, a better understanding of the interaction between these leukocytes and the tumor cells in vitro may eventually help one take measures to enhance this interaction in vivo. This could be of significance in the elimination of small tumor loads.